Abstract
Introduction: The mucopolysaccharidoses (MPS) are a group of 11 inborn errors of metabolism (IEM) which are part of the lysosomal storage diseases (LSDs). The MPS are multisystemic conditions that affect the entire body, with variations in the clinical presentation, having specific treatments available depending on the type of MPS. Nearly all MPS disorders compromise the osteoarticular system in different ways, and virtually all patients have abnormal urinary excretion of glycosaminoglycans (GAGs). MPS are rare diseases that are underdiagnosed due to health-care professionals’ lack of awareness, to poor access to screening and diagnostic methods, and to their extensive clinical heterogeneity. Attenuated forms may occur, which can make diagnosis of MPS even more difficult.
Methods: This study was conducted prospectively from March 2012 to January 2014 and included 55 patients at rheumatology and/or orthopedic services in Porto Alegre, Brazil. The screened patients presented with articular manifestations with no defined etiology. These patients were screened by quantitative and qualitative assessment of urinary GAGs.
Results and Discussion: Among the 55 cases investigated, one 15-year-old patient exhibited increased urinary GAG excretion; this patient was subsequently diagnosed with an attenuated form of MPS II, which was previously undetected.
Conclusion: Although the proportion of patients with MPS identified in the study sample was small (1/55), this study shows that these diseases are underdiagnosed and that systematic screening can help identify patients who may benefit from specific treatments already available for several MPS types.
Competing interests: None declared
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Cappelletti R, Del Rosso M, Chiarrugi VP (1979) A new electrophoretic method for complete separation of all known animal glycosaminoglycans in a monodimensional run. Anal Biochem 99:311–315
Cimaz R, Coppa GV, Koné-Paut I et al (2009) Joint contractures in the absence of inflammation may indicate mucopolysaccharidosis. Pediatr Rheumatol Online J 7:18
De Jong JG, Wevers RA, Liebrand-van Sambeek R (1992) Measuring urinary glycosaminoglycans in the presence of protein: an improved screening procedure for Mucopolysaccharidoses based on dimethylmethylene blue. Clin Chem 38:803–807
Giugliani R (2012) Mucopolysaccharidoses: from understanding to treatment, a century of discoveries. Genet Mol Biol 35:924–931
Hendriksz C (2011) Improved diagnostic procedures in attenuated mucopolysaccharidosis. Br J Hosp Med (Lond) 72:91–95
Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999) Prevalence of lysosomal storage disorders. JAMA 281:249–254
Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3421–3452
Pennock CA (1976) A review and selection of simple laboratory methods used for the study of glycosaminoglycan and the diagnosis of the mucopolysaccharidoses. J Clin Path 29:111–123
Poorthuis BJ, Wevers RA, Kleijer WJ et al (1999) The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 105:151–156
Acknowledgments
The authors are grateful to CNPq (Brazilian National Council for Scientific and Technological Development); to FIPE/HCPA; to the Medical Genetics Service of Hospital de Clinicas de Porto Alegre, particularly its Laboratory of Inborn Errors of Metabolism (LEIM); and to the MPS Brazil Network.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Additional information
Communicated by: Maurizio Scarpa, MD, PhD
Appendices
Synopsis
As attenuated forms of mucopolysaccharidoses may be difficult to identify, selective screening in patients with osteoarticular disease of unknown etiology may help to identify affected cases who could benefit from the specific therapies already available for several MPS types.
Contributions of the Individual Authors
TCRS interviewed the patients, obtained informed consent, collected the samples, and drafted the first version of the manuscript. CFMS, PL, MP, and IS referred patients for inclusion in the study, provided clinical information, and reviewed the final version of the manuscript. FB and MB performed the laboratory tests needed for screening and diagnosis and reviewed the final version of the manuscript. RG supervised the project, provided guidance in all steps, and revised the final version of the manuscript.
Compliance with Ethics Guidelines
Competing Interest Statement
RG received travel grants, speaker honoraria, and/or investigator fees from Actelion, Amicus, BioMarin, Genzyme, Shire, and Synageva; all other authors have no competing interests to disclose.
Details of Funding for All Authors
This study was supported by an institutional grant from FIPE/HCPA and by a research grant from CNPq/Brazil. RG received educational and research grants from Actelion, Amicus, BioMarin, Genzyme, Shire, and Synageva, which are not related to the present study. All other authors have no funding sources to disclose.
Details of Ethics Approval
This study was approved by the Institutional Review Board (GPPG/HCPA) in 17/07/2012, with the number 11-0557.
Rights and permissions
Copyright information
© 2015 SSIEM and Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
da Rocha Siqueira, T.C. et al. (2015). Screening for Attenuated Forms of Mucopolysaccharidoses in Patients with Osteoarticular Problems of Unknown Etiology. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 26. JIMD Reports, vol 26. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_484
Download citation
DOI: https://doi.org/10.1007/8904_2015_484
Received:
Revised:
Accepted:
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-49832-3
Online ISBN: 978-3-662-49833-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)